Reducing barriers to trauma inquiry in substance use disorder treatment – A cluster-randomized controlled trial

Background: Despite of the high rate of trauma in clients with substance use disorders, trauma often remains undetected in a majority of treatment-seeking clients. Improving professionals’ knowledge and competences in the inquiry of traumatic events is therefore of utmost importance to appropriately address the specific trauma-related treatment needs. However, professionals in substance use disorder treatment settings frequently report barriers to inquiring about traumatic events, e.g., the fear of offending or harming the client. Such barriers should be addressed by trainings to improve the systemtic inquiry of traumatic events in clients. Methods: In this cluster-randomized trial, we examined whether a one-day training in trauma inquiry (‘Learning How to Ask’) would reduce professionals’ perceived barriers to trauma inquiry. 148 professionals working in outpatient substance use disorder treatment centers were randomized to an intervention (n = 72) or a control group (n = 76). The professionals of the intervention group received a one-day training plus a refresher session 3 months later, the professionals of the control group received no training. Professionals rated their level of six common barriers to trauma inquiry on four-point Likert scales at baseline, at 3-month and 6-month follow-up, namely ‘Feeling uncomfortable when asking about traumatic events’, ‘Fear of offending the client’, ‘Fear of retraumatizing the client’, ‘Fear that client may terminate treatment’, ‘Unsure whether authorities have to be informed when perpetrator is known’, and ‘No trauma-specific treatment available’. Results: Five of the six perceived barriers to inquiring about traumatic events significantly decreased from baseline to 6-month follow-up to a greater extent in the trained group than in the control group (‘Feeling uncomfortable’: b = -0.32, 95% CI [-0.52, -0.12]; ‘Fear of offending the client’: b = -0.33, 95% CI [-0.56, -0.09]); ‘Fear of retraumatizing the client’: b = -0.45, 95% CI [-0.69, -0.22]; ‘Fear that client may terminate treatment’: b = -0.28, 95% CI [-0.49, 0.07]; ‘No trauma-specific treatment available’: b = -0.25, 95% CI [-0.51, -0.01]). Conclusions: Our findings provide first evidence that a one-day training in trauma inquiry is effective in reducing common barriers to trauma inquiry, which may improve detection of traumatic events

Fringe Projection Profilometry in Production Metrology: A Multi-Scale Comparison in Sheet-Bulk Metal Forming

Fringe projection profilometry in combination with other optical measuring technologies has established itself over the last decades as an essential complement to conventional, tactile measuring devices. The non-contact, holistic reconstruction of complex geometries within fractions of a second in conjunction with the lightweight and transportable sensor design open up many fields of application in production metrology. Furthermore, triangulation-based measuring principles feature good scalability, which has led to 3D scanners for various scale ranges. Innovative and modern production processes, such as sheet-bulk metal forming, thus, utilize fringe projection profilometry in many respects to monitor the process, quantify possible wear and improve production technology. Therefore, it is essential to identify the appropriate 3D scanner for each application and to properly evaluate the acquired data. Through precise knowledge of the measurement volume and the relative uncertainty with respect to the specimen and scanner position, adapted measurement strategies and integrated production concepts can be realized. Although there are extensive industrial standards and guidelines for the quantification of sensor performance, evaluation and tolerancing is mainly global and can, therefore, neither provide assistance in the correct, application-specific positioning and alignment of the sensor nor reflect the local characteristics within the measuring volume. Therefore, this article compares fringe projection systems across various scale ranges by positioning and scanning a calibrated sphere in a high resolution grid

Long-term outcomes of the pentaspline pulsed field ablation catheter for the treatment of paroxysmal atrial fibrillation: Results of the prospective, multicenter FARA-Freedom Study.

INTRODUCTION/OBJECTIVES Pulmonary vein isolation (PVI) is well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long term efficacy and safety data demonstrating single procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS FARA-Freedom, a prospective, non-randomized, multicenter study, enrolled patients with PAF undergoing de novo PVI with PFA, which were followed for 12 months with weekly transtelephonic monitoring (TTMs) and 72-hr Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success; which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. RESULTS The study enrolled 179 PAF patients (62 ± 10 yr, 39% female) at 13 centers. At index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20 min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high with 88.4% and 90.3% with weekly event and 72-hour Holter monitors, respectively. Freedom from composite primary effectiveness endpoint was 66.6%, 41 patients had atrial tachyarrhythmia recurrence: mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in 2 patients (1.1%), 1 tamponade and 1 TIA. There was no coronary spasm, PV stenosis, or AE fistula. There were 4 cases of transient phrenic nerve palsy, but all resolved during index procedure. CONCLUSIONS In this prospective, non-randomized, multicenter study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigorous endpoint definitions and high monitoring compliance and demonstrated favorable safety

Multi-national survey on the methods, efficacy, and safety on the post-approval clinical use of pulsed field ablation (MANIFEST-PF).

AIMS Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the 'real world' performance of the only approved PFA catheter, including acute effectiveness and safety-in particular, rare oesophageal effects and other unforeseen PFA-related complications. METHODS AND RESULTS This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7-291), full cohort included 1758 patients: mean age 61.6 years (range 19-92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9-100%). Procedure time was 65 min (38-215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). CONCLUSION In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of 'generic' catheter complications (tamponade, stroke) underscores the need for improvement

R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids

Background: R-flurbiprofen, one of the enantiomers of flurbiprofen racemate, is inactive with respect to cyclooxygenase inhibition, but shows analgesic properties without relevant toxicity. Its mode of action is still unclear. Methodology/Principal Findings: We show that R-flurbiprofen reduces glutamate release in the dorsal horn of the spinal cord evoked by sciatic nerve injury and thereby alleviates pain in sciatic nerve injury models of neuropathic pain in rats and mice. This is mediated by restoring the balance of endocannabinoids (eCB), which is disturbed following peripheral nerve injury in the DRGs, spinal cord and forebrain. The imbalance results from transcriptional adaptations of fatty acid amide hydrolase (FAAH) and NAPE-phospholipase D, i.e. the major enzymes involved in anandamide metabolism and synthesis, respectively. R-flurbiprofen inhibits FAAH activity and normalizes NAPE-PLD expression. As a consequence, R-Flurbiprofen improves endogenous cannabinoid mediated effects, indicated by the reduction of glutamate release, increased activity of the anti-inflammatory transcription factor PPAR gamma and attenuation of microglia activation. Antinociceptive effects are lost by combined inhibition of CB1 and CB2 receptors and partially abolished in CB1 receptor deficient mice. R-flurbiprofen does however not cause changes of core body temperature which is a typical indicator of central effects of cannabinoid-1 receptor agonists. Conclusion: Our results suggest that R-flurbiprofen improves the endogenous mechanisms to regain stability after axonal injury and to fend off chronic neuropathic pain by modulating the endocannabinoid system and thus constitutes an attractive, novel therapeutic agent in the treatment of chronic, intractable pain

HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection

Nucleoside analogs (NAs) are used to treat numerous viral infections and cancer. They compete with endogenous nucleotides (dNTP/NTP) for incorporation into nascent DNA/RNA and inhibit replication by preventing subsequent primer extension. To date, an integrated mathematical model that could allow the analysis of their mechanism of action, of the various resistance mechanisms, and their effect on viral fitness is still lacking. We present the first mechanistic mathematical model of polymerase inhibition by NAs that takes into account the reversibility of polymerase inhibition. Analytical solutions for the model point out the cellular- and kinetic aspects of inhibition. Our model correctly predicts for HIV-1 that resistance against nucleoside analog reverse transcriptase inhibitors (NRTIs) can be conferred by decreasing their incorporation rate, increasing their excision rate, or decreasing their affinity for the polymerase enzyme. For all analyzed NRTIs and their combinations, model-predicted macroscopic parameters (efficacy, fitness and toxicity) were consistent with observations. NRTI efficacy was found to greatly vary between distinct target cells. Surprisingly, target cells with low dNTP/NTP levels may not confer hyper-susceptibility to inhibition, whereas cells with high dNTP/NTP contents are likely to confer natural resistance. Our model also allows quantification of the selective advantage of mutations by integrating their effects on viral fitness and drug susceptibility. For zidovudine triphosphate (AZT-TP), we predict that this selective advantage, as well as the minimal concentration required to select thymidine-associated mutations (TAMs) are highly cell-dependent. The developed model allows studying various resistance mechanisms, inherent fitness effects, selection forces and epistasis based on microscopic kinetic data. It can readily be embedded in extended models of the complete HIV-1 reverse transcription process, or analogous processes in other viruses and help to guide drug development and improve our understanding of the mechanisms of resistance development during treatment

A worldwide survey on incidence, management and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: The POTTER-AF study.

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management and outcome are sparse. METHODS AND RESULTS This international multicenter registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553,729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed at 214 centers in 35 countries. In 78 centers 138 patients (0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (p<0.0001)) were diagnosed with an oesophageal fistula. Periprocedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8%, and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) (odds ratio 7.463 (2.414, 23.072) p<0.001). CONCLUSIONS Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high